Abnormalities in red blood cell (RBC) cation permeability and cellular hydration are seen with many hemolytic disorders. The altered membrane physiology has been elucidated in a few of these disorders, but in virtually all cases, specific membrane structural abnormalities remain to be defined. Studies proposed here will further define the relationship between altered cation permeability, cellular hydration, and membrane protein-lipid interactions. These studies are divided into four parts. (1) Pathophysiology of RBC K-loss and cellular dehydration will be compared in RBC's from patients with hereditary hemolytic anemias (hereditary xerocytosis, pyruvate kinase deficiency), and several in vitro models. These studies will characterize membrane perturbations which modify K permeability, identify the physiologic effects of K and water loss, and evaluate changes in membrane protein-lipid organization. (2) Pathophysiology of increased Na and K permeability will be compared in RBC's from patients with hemolytic anemias (hereditary stomatocytosis, sickle cell anemia), Heinz body-containing RBC'S, propranolol-treated cells, and RBC's with specific alterations in membrane proteins. These studies will characterize the metabolic, permeability, and membrane structural abnormalities in these RBC's. (3) The cation requirements for amino acid transport will be characterized in human reticulocytes, and the role of cation-amino acid cotransport as a determinant of RBC hydration will be evaluated. (4) Cation permeability and volume regulation will be studied in RBC's from dogs with hereditary hemolytic anemias (pyruvate kinase deficiency, herditary stomatocytosis), and in dog RBC's treated with drugs (propranolol, acetylphenylhydrazine).